Anthracyclines, and more specifically, doxorubicin, daunorubicin, carminomycin and aclacinomycin have emerged in recent years as important chemotherapeutic agents in the treatment of a broad spectrum of human cancers. Doxorubicin and daunorubicin, particularly, appear to be most useful and widely used drugs in the treatment of an unusually large number and wide variety of solid tumors and leukemias. Other drugs used in the treatment of various cancers include chlorambucil, cyclophosphamide, methotrexate, 5-uracil, arabinosyl cytosine, mitomycin, cis-platinum 11 diamine dichloride, procarbazine, vinblastine vincristine and the like. The therapeutic effect of these drugs is believed to be based on their interaction with DNA in the cell. However, chronic treatment of patients with these drugs produces irreversible heart damage and other serious complications which can be fatal if the treatment continues.
The treatment of cancer is extremely dose dependent. A 10% deficiency in the required dosage may produce no effect on the cancer while a 10% excess over the required dosage can produce serious ill effects or even death. Thus, there is a great need for measuring the therapeutic levels of these drugs in biological fluids.
U.S. Pat. No. 4,559,299 issued December 17, 1985 to Boris M. Rotman, entitled "Cytotoxicity Assays In Cell Culturing Devices", discloses a method and devices for predicting the in vivo responsiveness of cancerous cells to cytotoxic agents based on in vitro culture assessments.
U.S. Pat. No. 4,610,869 issued September 9, 1986 to Arthur E. Bogden, entitled "Method For In Vivo Testing Of Biological Response Modifiers Including Monoclonal Antibodies", describes an in vivo method for measuring the ability of biological response modifiers, including monoclonal antibodies, to interact with tumor tissue. Following the implantation of a fresh, surgical tumor in a host organism and administering to the host organism a predetermined dose of a biological response modifier, the degree of interaction between the biological response modifier and the tumor tissue is determined.
U.S. Pat. No. 4,419,340 issued December 6, 1983 to Seymour Yolles, entitled "Controlled Release Of Anti-cancer Agents From Biodegradable Polymers", describes an article and a method for controllably dispensing anti-cancer agents. The article describes biodegradable polymer shapes which contain one or more of the anti-cancer agents.
Other methods nave also been devised for the use of intercalating dyes in the detection of DNA in the cell.
In recent years, fiber optics, lasers, chemical reactions, optics and spectroscopy have been integrated to produce the new concept of remote fiber spectroscopy. This concept enables the development of small, ductile probes to detect and monitor certain chemical components in certain biological and the ambient environment. At the heart of the concept is the development of the "optrode", a fiber terminal with preselected chemical and physical properties. A single fiber is used for both excitation and for collection of the return signal, thereby keeping the sensor small and optically simple.
The general design and construction of the basic optrode is described and claimed in U.S. Pat. No. 4,577,109 issued Mar. 18, 1986 to Tomas Hirschfeld. Although, from a theoretical point of view, optrodes provide a great deal of geometric flexibility and make it possible to perform in situ, in vitro or in vivo analyses using optical spectroscopy without a line of sight, from a practical side, however, there are only a very limited number of chemical reactions which lend themselves to fiber optic spectrometry and which meet the stringent requirements for a good sensor where no preparation of the sample is possible, as is the case with in situ, in vitro or in vivo measurements. In the design of the sensor, therefore, several factors need to be taken into consideration. These factors include but are not limited to the selection of an appropriate chemical reaction which is amenable to fiber optical spectrometry, the feasibility of immobilizing or fixing the necessary reagents at one end of the optical fiber, the possible interference or disabling of the optrode by extraneous components of the sample matrix and the active shelf life of the particular optrode impregnated with the active ingredients. Therefore, selection, adaptation or development of the chemistry from the laboratory scale to the micro scale of the optrode is very complex and is thus the limiting step in the construction and development of the suitable optrode.
U.S. Pat. No. 4,488,814 issued December 18, 1984 to Leighton C. Johnson and entitled "Apparatus For And Method Of Optical Absorbance And Fluorescent Radiation Measurement", relates to an apparatus and method for optical absorbance or radiation measurement of liquid samples.
Accordingly, it is an object of the present invention to provide for the in vivo measurement of the dose critical levels of anti-cancer drugs in biological fluids.
Another object of the invention is to provide an apparatus that can be used for the in vivo or in vitro measurement and monitoring of the dose critical levels of anti-cancer drugs in biological fluids.
Yet another object is to provide a method for the continuous monitoring of the levels of anti-cancer drugs in the blood of human patients.
Another object is to monitor simultaneously multiple samples of biological fluids to measure the levels of anti-cancer drugs.
Additional objects, advantages and novel features of the invention will be set forth in part in the description which follows, and in part will become apparent to those skilled in the art upon examination of the following or may be learned by practice of the invention. The objects and advantages of the invention may be realized and attained by means of the instrumentalities and combinations particularly pointed out in the appended claims.